The objective of this study was to investigate the spatial distribution of reported hantavirus cases in São Paulo State, Brazil (n = 80), from 1993 to 2005 and identify local climatic patterns during this period. Kernel point estimation of density was used to show the highest concentrations in Ribeirão Preto, São Carlos, Franca, Tupi Paulista, and Greater São Paulo. Increase in the number of cases during this period suggests disease dissemination even when considering increased diagnostic capacity and higher sensitivity of the health services. There was a marked seasonal variation in hantavirus in the cerrado (savannah) areas; the common pattern is a higher incidence in drier months as compared to mean levels in the last 40 years. These coincide with periods of high rodent food source levels in grains, sugarcane, and other crops. Harvesting and storing grains increases human exposure to rodents. Climatic indicators together with ecological variables can be local transmission risk markers and should receive more attention in epidemiological monitoring and control of the disease.